井冈羟胺A的衍生及其生物活性研究
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摘要
井冈霉素是高效、安全和作用机制独特的无公害生物农药，其水解产物井冈羟胺A是已知天然海藻糖酶抑制剂中抑酶活性最高的化合物之一。本论文选取井冈羟胺A为先导化合物进行优化研究，设计合成了40个未见文献报道的新化合物，并对它们进行了杀虫、杀菌和除草等生物活性的测试。
首先，对制备井冈羟胺A的方法进行了改进，以井冈霉素A为原料，改用碳酸钙为中和试剂，采用在中和液中直接结晶的方法，得到了纯度较好的井冈羟胺A盐酸盐，收率达到了50％。制备步骤简洁，分离简单。
用二甲菊酰氯、二氯菊酰氯和功夫菊酰氯对井冈羟胺A的C-7’位上的羟基进行结构改造，合成了3个新的7’-O-菊酰基井冈羟胺A。对实验条件进行了优化。产物用水和乙酸乙酯两相分离，水相经两次柱层析，得到目标产物，收率为43.3～44.3％。
采用活性二氧化锰对井冈羟胺A的C-7’位上的羟基进行选择性氧化，得到了7’-井冈羟胺A醛，反应采用超声波辐射催化，取得了较好的效果，收率达77.8％。
用脂肪胺和芳胺对7’-井冈羟胺A醛的醛基进行修饰，合成7个新的7’-(N-取代亚胺基)井冈羟胺A。其中化合物7’-(N-十二烷基亚胺基)井冈羟胺A的脂溶性较母体化合物有了较大的改善。
在对甲苯磺酸催化下，对井冈羟胺A的C-4，7，4’，7’位羟基进行了缩醛(酮)化反应，合成了29个新的井冈羟胺A-4，7，4’，7’-二缩醛(酮)衍生物。在实验中，对催化剂的用量和反应物的投料比进行了优化，在最优条件下，目标产物收率为32％左右。
初步建立了针对井冈羟胺A衍生物的分离方法，即将反应产物以水和乙酸乙酯两相分离，低取代产物主要存在于水相，水相浓缩后以醇萃取，醇溶液浓缩后经柱层析二次分离，可得到纯度约80％左右的产物；多取代产物主要存在于酯相，浓缩后可经多次薄板层析或柱层析分离，得到纯度约85％左右的产物。
对所有井冈羟胺A衍生物均进行了生物活性测定，结果表明，在井冈羟胺A
Validamycins are safe and highly effective bio-pesticides with special modes of action. Validoxylamine A is the aglycone of the validamycin A, which exhibits a very strong competitive inhibitory activity against trehalases. Forty new compounds of validoxylamine A derivatives were prepared based on validoxylamine A as the leading compound. Their bioactivities of insecticidal, fungicidal and herbicidal activity were studied.
Firstly, validoxylamine A was prepared by hydrolysis of validamycin A through the improved method of synthesis. Calcium carbonate was used as the neutralizing agent and validoxylamine A was crystallized directly from the neutralized solution. The yield of validoxylamine A was 50%. The purity was good. The process of synthesis and the separate method were simple.
Three new 7'-O-chrysanthemylvalidoxylamine A were prepared in 43.3～44.3% yields by optimizing the reaction time and the molar ratio of reactants. The products were separated by twice column chromatography.
7'-aldehyde validoxylamine A was prepared by the reaction of selective oxidation. The hydroxyl in the C-7' position of validoxylamine A was oxidated by active manganese dioxide under ultrasonic radiation. It was easy to operate and the yield was 77.8 %
Seven new 7'-imino-validoxylamine A derivatives were synthesized by the reaction of 7'-aldehyde validoxylamine A and arylamines or alkylamines. 7'-(N-dodecylimino)validoxylamine A , which is better than the leading compound, can dissolve in organic solvent such as ethyl acetate
In the presence of p-toluenesulphonic acid, twenty-nine of acetals or ketals derivatives of validoxylamine A were prepared from validoxylamine A. The yield was about 32% by optimizing the scalar of catalyzer and the molar ratio of reactants.
Preliminary method of separating validoxylamine A derivatives was found. The
首先，对制备井冈羟胺A的方法进行了改进，以井冈霉素A为原料，改用碳酸钙为中和试剂，采用在中和液中直接结晶的方法，得到了纯度较好的井冈羟胺A盐酸盐，收率达到了50％。制备步骤简洁，分离简单。
用二甲菊酰氯、二氯菊酰氯和功夫菊酰氯对井冈羟胺A的C-7’位上的羟基进行结构改造，合成了3个新的7’-O-菊酰基井冈羟胺A。对实验条件进行了优化。产物用水和乙酸乙酯两相分离，水相经两次柱层析，得到目标产物，收率为43.3～44.3％。
采用活性二氧化锰对井冈羟胺A的C-7’位上的羟基进行选择性氧化，得到了7’-井冈羟胺A醛，反应采用超声波辐射催化，取得了较好的效果，收率达77.8％。
用脂肪胺和芳胺对7’-井冈羟胺A醛的醛基进行修饰，合成7个新的7’-(N-取代亚胺基)井冈羟胺A。其中化合物7’-(N-十二烷基亚胺基)井冈羟胺A的脂溶性较母体化合物有了较大的改善。
在对甲苯磺酸催化下，对井冈羟胺A的C-4，7，4’，7’位羟基进行了缩醛(酮)化反应，合成了29个新的井冈羟胺A-4，7，4’，7’-二缩醛(酮)衍生物。在实验中，对催化剂的用量和反应物的投料比进行了优化，在最优条件下，目标产物收率为32％左右。
初步建立了针对井冈羟胺A衍生物的分离方法，即将反应产物以水和乙酸乙酯两相分离，低取代产物主要存在于水相，水相浓缩后以醇萃取，醇溶液浓缩后经柱层析二次分离，可得到纯度约80％左右的产物；多取代产物主要存在于酯相，浓缩后可经多次薄板层析或柱层析分离，得到纯度约85％左右的产物。
对所有井冈羟胺A衍生物均进行了生物活性测定，结果表明，在井冈羟胺A
Validamycins are safe and highly effective bio-pesticides with special modes of action. Validoxylamine A is the aglycone of the validamycin A, which exhibits a very strong competitive inhibitory activity against trehalases. Forty new compounds of validoxylamine A derivatives were prepared based on validoxylamine A as the leading compound. Their bioactivities of insecticidal, fungicidal and herbicidal activity were studied.
Firstly, validoxylamine A was prepared by hydrolysis of validamycin A through the improved method of synthesis. Calcium carbonate was used as the neutralizing agent and validoxylamine A was crystallized directly from the neutralized solution. The yield of validoxylamine A was 50%. The purity was good. The process of synthesis and the separate method were simple.
Three new 7'-O-chrysanthemylvalidoxylamine A were prepared in 43.3～44.3% yields by optimizing the reaction time and the molar ratio of reactants. The products were separated by twice column chromatography.
7'-aldehyde validoxylamine A was prepared by the reaction of selective oxidation. The hydroxyl in the C-7' position of validoxylamine A was oxidated by active manganese dioxide under ultrasonic radiation. It was easy to operate and the yield was 77.8 %
Seven new 7'-imino-validoxylamine A derivatives were synthesized by the reaction of 7'-aldehyde validoxylamine A and arylamines or alkylamines. 7'-(N-dodecylimino)validoxylamine A , which is better than the leading compound, can dissolve in organic solvent such as ethyl acetate
In the presence of p-toluenesulphonic acid, twenty-nine of acetals or ketals derivatives of validoxylamine A were prepared from validoxylamine A. The yield was about 32% by optimizing the scalar of catalyzer and the molar ratio of reactants.
Preliminary method of separating validoxylamine A derivatives was found. The
引文
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